Protein drugs have proven themselves as highly important therapeutic drugs in treating various diseases, including cancer and cardiovascular diseases. The benefits of various antibodies for treating cancers are well known. One of the major problems with protein drugs is their short half life in blood circulation. The drug delivery formations that can deliver protein drugs for long-term, ranging from weeks to months, will provide a basic tool for delivering a variety of protein drugs, enabling the sustained and powerful impact to the field. Particulate formulations in the micro-sizes (microparticles) have been extensively studied for long-term delivery of low molecular weight drugs, but their success with protein drugs has been extremely limited. The deficiencies of the current particulate formulations prepared by the emulsion methods include heterogeneous particle size, low drug loading capacity, high initial burst release, incomplete drug release, and difficulty in scaling-up production. The goal of this research is to use the recently developed hydrogel template approach to formulate homogeneous microparticles for long-term (1 month ~ 3 months) delivery of protein drugs for clinical applications. The hypothesis in this proposal is that the hydrogel template-based fabrication provides particles of high drug loading with predictable release profiles by confining the protein/PLGA mixture to the micro wells in a hydrogel template during the microencapsulation process. The specific aims of this project are: (i) to fabricate homogeneous nan0/micro structures using hydrogel templates; (ii) to characterize protein loading and release properties of nan0/micro structures; and (iii) to evaluate therapeutic effects by in vivo animal study and in vitro cell culture method. The innovation in the hydrogel template approach is that microparticles, which are fabricated inside individual wells of the hydrogel template, can be harvested by simply dissolving the template in water. Currently, no other fabrication methods allow such an easy way of harvesting the formed microparticles. The simplicity in the method allows easy scale-up production for clinical applications. The significance of this research is that the hydrogel template approach provides a new general method of precise fabrication of microparticles with predefined properties for protein drug delivery. The hydrogel template method is an enabling technique that can be applied to all types of drugs, making it easy to develop clinically useful formulations for various protein drugs.